EW-7197 Hydrochloride, CAS No. 1352610-25-3, is a highly potent, selective, and orally bioavailable inhibitor of TGF-β type 1 receptor kinase.

Product information

CAS Number: 1352610-25-3

Molecular Weight: 435.88

Formula: C22H19ClFN7

Synonym:

EW-7197 HCl

Vactosertib Hydrochloride

Chemical Name: N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline hydrochloride

Smiles: Cl.CC1=CC=CC(=N1)C1NC(CNC2=CC=CC=C2F)=NC=1C1=CN2N=CN=C2C=C1

InChiKey: UDRJLVATGDHMJM-UHFFFAOYSA-N

InChi: InChI=1S/C22H18FN7.ClH/c1-14-5-4-8-18(27-14)22-21(15-9-10-20-25-13-26-30(20)12-15)28-19(29-22)11-24-17-7-3-2-6-16(17)23;/h2-10,12-13,24H,11H2,1H3,(H,28,29);1H

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

EW-7197 Hydrochloride (10-1000 nM; 30 minutes; 4T1 cells) treatment blocks the TGFβ-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner in 4T1 cells. EW-7197 Hydrochloride suppresses the TGFβ-induced nuclear translocation of Smad2/3 in 4T1 cells and MCF10A cells. The IC50 value of EW-7197 Hydrochloride on pSmad3 in 4T1 cells is 10-30 nM. EW-7197 Hydrochloride abrogates TGFb1-induced tumor cell migration and invasion. TGFβ1 downregulated the mRNA level of CDH1 and upregulated the mRNA levels of FN1, HMGA2 (high-mobility group AT-hook 2), SNAI1, and SNAI2 (Snail family zinc finger 1 and 2, respectively). Moreover, EW-7197 Hydrochloride abolishes the TGFβ1-induced effects on genes related to epithelial-to-mesenchymal transition (EMT).

In Vivo:

EW-7197 Hydrochloride (40 mg/kg; intraperitoneal injection; every other day; for 10 weeks; MMTV/c-Neu female mice) treatment inhibits Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice. EW-7197 Hydrochloride also inhibits the epithelial-to-mesenchymal transition (EMT) in both TGFβ-treated breast cancer cells and 4T1 orthotopic-grafted mice. Furthermore, EW-7197 Hydrochloride enhances cytotoxic T lymphocyte activity in 4T1 orthotopic-grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor-bearing mice.

References:

1. Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, Park SJ, Park HJ, Lee K, Sheen YY, Kim DK. Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2 -yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent. J Med Chem. 2014 May 22;57(10):4213-38. doi: 10.1021/jm500115w. Epub 2014 May 13. PubMed PMID: 24786585.

Products are for research use only. Not for human use.